“Successive transition from one paradigm to another via revolution is the usual developmental pattern of a mature science.”

In other words, a science has growing pains and is bound to have a fair bit of debate and controversy, until a new paradigm becomes dominant. I think that there is a current – in part prompted by the power of socio-professional media which has allowed minds to connect and knowledge to spread – that will see many of the things that are now “Standard of Care” out the door.

So first of all, the following are must-listens, the first a lecture by Paul Marik, whom I have had the chance to collaborate with in the last years and respect greatly, on knowledge, experience, and even more on his refusal to take anything for granted and being in a seemingly-constant quest for the improvement of medicine.

The second link is Scott Weingart’s take on it, which I think is equally awesome.

I think Paul is pushing the envelope in an essential way, and Scott does a fantastic job of seeing or putting it in perspective. Enjoy:

My (very) humble opinion on this is a rather simple, almost philosophical one: why are we seemingly obsessed with treating a predominantly vasodilatory pathology with large amounts of volume? I’ve said this in previous posts and podcasts, but this, in my opinion, is largely cultural and dogmatic. “Levophed – Leave’em dead” is something I heard as a student and resident, and came to take for granted that I should give lots of fluid in hopes of avoiding pressors… But there’s no evidence at all to support this. The common behavior of waiting until someone has clearly failed volume resuscitation before starting pressors befuddles me (think how long it takes to get two liters of fluid in most ERs…). If I was in that bed, I’d much rather spend an hour a bit “hypertensive” (eg with a MAP above 70) than a bit hypotensive while awaiting final confirmation that I do, in fact, need pressors.

I strongly suspect that it’s just a matter of improving vascular tone, giving some volume (which may be that 3 liter mark), and ensuring that the microcirculation/glycocalyx is as undisturbed as possible. Now when I say it may be the 3 liters, I firmly believe this will not apply to everyone, and that it will be 1 liter in some, and 4 in others, and that a recipe approach will be better than nothing, but likely harm some.

I think that blind (eg no echo assessment) of shock is absurd, and for anyone to propose an algorithm that does not include point-of-care ultrasound is only acceptable if they are in the process of acquiring the skill with the intention of modifying their approach in the very near future.

The whole microcirculation/glycocalyx is absolutely fascinating stuff, and undoubtedly will come under scrutiny in the next few years, and it is definitely something I will focus on in upcoming posts & podcasts. Our resuscitation has been macro-focused, and certainly it is time to take a look at the little guys, who might turn out to have most of the answers. For instance, there is some remarkable data on HDAC inhibitors (common valproic acid) and their salutatory effects in a number of acute conditions such as hemorrhagic shock (Dr. Alam) which have nothing to do with macro-resuscitation, and everything to do with cell signaling and apoptosis. Hmmm…

First of all, lets look at it from a theoretical perspective. How would steroids contribute to ROSC (return of spontaneous circulation)? Hard to believe they possibly could, given the ultra-short timeframe to ROSC – minutes mostly – and the much longer action of steroids. However, it is quite possible – and in view of this study perhaps likely – that there is an effect on shock and RONF (return of neurological function).

Why? Post arrest shock results in MSOF due to a cascade of inflammation resulting from the hypoxic insult. Remember that we are not designed to survive these events. Being designed to fight off moderate trauma and infection (eg being bitten by an animal or clubbed by another caveman) our physiological reaction often overshoots the mark resulting in more damage than good, as it does in sepsis (variably depending on our different geno/phenotypes). So whether liver, kidney or brain damage, some component is not only related to pure hypoxia but also to an inflammatory cascade that has a prolonged effect. This is the same thing we are targeting with cooling, on top of a simple metabolic supply/demand issue, so in terms of biological plausibility, it makes some sense.

In the post-ROSC phase, there is always the possibility of relative adrenal insufficiency – after all, the adrenals have taken a hit as all the other organs did – so again there is biological plausibility.

There’s quite a bit of debate out there as to whether or not to apply this. I’m pragmatic, not a purist, and my beliefs lie in evidence, biological plausibility and the risk/benefit ratio. In this case, I think the decision is actually quite simple. The way I see it, the steroids are harmless and probably helpful, so I have been giving solumedrol in the last few months.

If anything, I’m more concerned about the harm I may be doing with epinephrine/vasopressin, especially in terms of RONF. I do hope an epi (various doses) vs placebo study is done, because it is difficult to withhold, knowing that there is greater immediate effect on ROSC… Hard decision as the clinician at the bedside, and hopefully this will become clearer in the near future.

For those unclear about the whole epi debate, the physiological issue is that the relationship between pressure and perfusion is represented by an inverted U curve – at very high pressures (from vasoconstriction) perfusion is decreased (think of the extremities on high dose pressers with a decent BP). So although we may help coronary perfusion pressure and thus ROSC, end-organ damage is greater…and nothing matters much without a brain.

So bottom line: I’d go ahead with the steroids, and for now the V and E, but I wouldn’t be surprised to drop or decrease those soon.

More to come on resuscitation and its future (the present for some of us…) in posts and podcasts!